Double fiber bundle dialyzer

ABSTRACT

A dialyzer composed of: first and second dialyzation chambers, and an intermediate chamber interposed between the first and second dialyzation chambers. Each dialyzation chamber has opposed first and second ends and contains a filter member that separates the chamber into a blood compartment and a dialysate compartment. Each of the compartments extends between first and second ends. Each of the chambers has a respective one of a blood inlet or outlet and a dialysate inlet or outlet arranged so that blood and dialysate flow in counter-current to one another in both chambers. The intermediate chamber is connected to form a dialysate-free blood flow passage between the blood compartments.

CROSS-REFERENCE TO RELATED APPLICATION

Applicant claims priority rights for Provisional Application No.61/080,769, filed on Jul. 15, 2008, the disclosure of which isincorporated herein by reference.

STATEMENT REGARDING FEDERALLY SPONSORED RESEARCH OR DEVELOPMENT

This invention was made with government support under 5R42DK64500awarded by National Institutes of Health (NIH), Bethesda, Md. Thegovernment has certain rights in the invention.

BACKGROUND OF THE INVENTION

The present invention relates to dialyzers, and particularly single-unitdialyzers that can be used with all existing dialysis equipment toprovide dialytic therapies having increased efficiency.

BRIEF SUMMARY OF THE INVENTION

A dialyzer according to the invention is composed of two bundles ofhollow fibers constituted by semi-permeable membranes, preferably housedwithin a single casing that delimits, in effect, two chambers. Thedialyzer further includes an intermediate chamber in which blood flowsfrom one fiber bundle to the other so that the blood coming from thefirst fiber bundle becomes intermixed and thus homogenized. Thisdialyzer is arranged to be connected to a standard dialysis machine viaa blood inlet and outlet and a dialysate inlet and outlet. No additionalconnections are required.

BRIEF DESCRIPTION OF THE DRAWING

FIG. 1 is a simplified, elevational, pictorial view of one preferredembodiment of a dialyzer according to the invention.

FIG. 2 is an elevational, cross-sectional view of the casing accordingto a preferred embodiment of the invention.

FIG. 3 is an elevational, cross-sectional view of top header caps of adialyzer according to the invention.

FIG. 4 is an elevational, cross-sectional view of a bottom header cap ofa dialyzer according to the invention, viewed in the direction ofcross-section line 4-4 in FIG. 5.

FIG. 5 is a top plan view of the header cap of FIG. 4.

FIGS. 5A-5E are cross-sectional views viewed in the direction ofcross-section lines 5A-5A, 5B-5B, 5C-5C, 5D-5D and 5E-5E, respectively,in FIG. 5

DETAILED DESCRIPTION OF THE INVENTION

FIG. 1 shows one preferred embodiment of the invention, which can bedelineated as a double fiber bundle dialyzer. This apparatus iscomposed, in effect, of an outer casing that delimits two dialyzationchambers 2, 4 that may be disposed, effectively, side by side. Eachdialyzation chamber 2, 4 is closed off by a respective part of the outercasing and manifolds 24, 26, 28, to be described below. Each dialyzationchamber contains a filter member in the form of a bundle 12, 14,respectively, of semi-permeable hollow membrane fibers. Each fiber hasthe form of a small diameter hollow tube. The outer casing parts have acommon wall 20, the common wall being provided, near the bottom of theouter casing, with an opening 22 forming a constricted passage fordialysate.

Manifold 24 is provided with openings that place the upper ends of thefibers of bundle 12 in communication with a blood outlet compartment 30,while manifold 26 is provided with openings that place the upper ends ofthe fibers of bundle 14 in communication with a blood inlet compartment34. Compartments 30 and 34 are delimited by header caps.

Manifold 28 is provided with openings that place the lower ends of thefibers of bundles 12 and 14 in communication with an intermediatechamber 38 in which blood flows from the fibers of bundle 14 to thefibers of bundle 12 while blood from the various fibers becomeintermixed so that the blood entering the fibers of bundle 12 is of amore uniform composition. The component delimiting chamber 38 may be afurther header cap.

Manifolds 24, 26 and 28 close off the portions of each chamber 2, 4through which dialysate flows so that dialysate cannot flow into chamber38.

FIG. 2 is a cross-sectional view of one preferred embodiment of theouter casing of a dialyzer according to the present invention. Thisembodiment is composed essentially of two circularly cylindrical tubesdelimiting the dialyzation chambers 2, 4. Common wall 20 with opening 22is provided at the lower end of the outer casing. By way of example,opening 22 may have a circular cross section with a diameter of theorder of 1.4 mm and a longitudinal axis that has a length of the orderof 6.6 mm and is inclined at an angle of the order of 60°-85° to thelongitudinal axis of each chamber 2, 4 and oriented to produce a flowhaving a direction with a component parallel to the direction ofdialysate flow in chamber 4.

Also by way of example, the overall length of the outer casing may be ofthe order of 28.6 cm and the distance between the longitudinal axes ofchambers 2 and 4 may be of the order of 5.2 cm.

The diameter of each chamber 2, 4 is of the order of 3.6 cm at thecenter of the chamber. However, other diameter values can be used. Ingeneral, the diameter of the chamber will be related to the size of thefiber bundle. As a rule of thumb, the total area of the fibers in abundle, based on the outer diameters of all of the fiber OD in oneplane, should preferably be approximately 50-55% of the cross-sectionalarea of the chamber in the same plane.

The locations of manifolds 24, 26 and 28 are shown in broken lines inFIG. 2.

FIG. 3 shows an example of top header caps delimiting compartments 30and 34.

FIGS. 4, 5 and 5A-5E show an example of the bottom header cap delimitingcompartment 38.

Some exemplary dimensions are shown in FIGS. 2, 4 and 5A-5E. The bottomheader cap is provided with a channel 60 designed to aid blood flow fromfiber bundle 14 to fiber bundle 12. The dimensions of channel 60 are ofthe order of 10.5 mm wide and 5.3 mm high and the radius of curvature ofchannel 60 is also 5.3 mm. Channel 60 extends essentially between themidpoints of the two halves of the header cap. This provides a path forthe blood to travel and mix while minimizing the pressure drop wherechamber 38 narrows between fiber bundles. The top part is curved but thebottom forms a semicircle or “D shape” with the flat top of themanifold.

The volumes enclosed by the fibers of bundles 12 and 14 definerespective blood compartments in chambers 2 and 4, while the volumessurrounding the fibers of bundles 12 and 14 define respective dialysatecompartments in chambers 2 and 4.

Manifolds 24, 26 and 28 constitute walls that close off the upper endsof the dialysate compartments and manifold 28 constitutes a wall thatclose off the lower ends of the dialysate compartments. The lower end ofcommon wall 20 bounds a constricted passage between the two dialysatecompartments.

Compartment 34 is provided with an inlet passage 40 for the delivery ofblood into the apparatus, while compartment 30 has a blood outlet 42 forremoval of blood from the apparatus. In addition, chamber 2 is providedwith a dialysate inlet 44, while chamber 4 is provided with a dialysateoutlet 46.

During a dialysis procedure, fresh dialysate is introduced through inlet44 into the dialysate compartment in chamber 2, flows through opening,or restricted passage, 22 near the bottom of common wall 20 into thedialysate compartment in chamber 4, and then out through outlet 46. Atthe same time, blood that is to be dialyzed is introduced into chamber34 via inlet 40, flows through the fibers of bundle 14 into intermediatechamber 38, and then flows through the fibers of bundle 12 to chamber 30and finally exits the apparatus through outlet 42.

In chamber 4, plasma water is removed from blood flowing through thefibers of bundle 14 and is transferred into the dialysate compartment inchamber 4 by being filtered across the semipermeable membranes formingthe walls of the fibers of bundle 14.

Upon exiting the blood compartment in chamber 4, the blood enters andflows through intermediate chamber 38 and then into the bloodcompartment in chamber 2. The function of intermediate chamber 38 willbe described below.

As the blood flows through the blood compartment in chamber 2, i.e.,through the fibers of bundle 12, fresh dialysate is filtered from thedialysate compartment, across the semipermeable membranes forming thewalls of the fibers of bundle 12 and into the blood compartment ofchamber 2 at a rate substantially equal to the rate at which plasmawater was filtered from the blood compartment of chamber 4. The mannerin which the filtration rates are controlled will be described below.

Thus, ultrafiltration is performed in chamber 4, while substitutionfluid is introduced from fresh dialysate into the blood compartment inchamber 2 via backfiltration. The dialyzer is thus capable of achievinga high rate of ultrafiltration with the introduction of substitutionfluid by backfiltration that results in an on-line Hemodiafiltration(HDF) treatment. HDF is a hemodialysis modality that combines the use ofdialysis fluid for the diffusive removal of toxins with larger volumesof ultrafiltration (compared to standard hemodialysis) to remove middleweight molecules by convection.

Fresh dialysate fluid for this system may be generated using existingmethods and standard dialysis equipment. The dialysate fluid enters thedialysate compartment in chamber 2 and flows in counter-current withrespect to the blood flow. This dialysate fluid performs twofunctions: 1) it acts to set up a concentration gradient relative to theblood compartment, thereby inducing diffusion of solutes across thesemi-permeable membranes from the blood compartment to the dialysatecompartment in chamber 2; and 2) because of the relatively higherpressure of the incoming dialysate compared to the blood compartmentpressure, it produces a backfiltration of dialysate into the bloodcompartment.

Upon exiting chamber 2, the dialysate fluid enters the dialysatecompartment in chamber 4, still flowing in counter-current with respectto the blood flow in the respective blood compartment. The dialysateflow rate increases as the dialysate flows through the dialysatecompartment in chamber 4, due to filtration of plasma water from theblood compartment across the semi-permeable membranes of the fibers ofbundle 14.

Dialysate also flows around the fibers of each fiber bundle, entering atone side of the respective dialysate chamber and flowing diagonallyacross the chamber and around the membrane fibers before exiting at theother side, and the other end, of the respective chamber. This flowacross, or around, both fiber bundles may enhance fiber surface contactand diffusive removal of substances.

Upon exiting the dialyzer, the spent or used dialysate is transportedback to the dialysis machine and to the drain in a conventional manner.

The fibers of both bundles may be of the same material and both bundlesalso have the purpose of diffusive removal of toxins. It is alsopossible, at high protein concentrations in the blood, that somebackfiltration starts in fiber bundle 14.

The volumetric control of a dialysis machine ensures properultrafiltration and controls the rates of filtration and backfiltration.The fiber bundle involved in the backfiltration, in chamber 2, acts as afinal fluid quality filter and has been shown to bring both bacteria andendotoxin to levels that approach pharmaceutical grade fluids.

The advantage of this system is that small molecules such as urea can beremoved efficiently due to the appropriately large surface area of thetwo fiber bundles, and midsized molecules are removed efficiently due tothe large filtration with backfiltration, which is optimized with thisdouble fiber bundle configuration. No additional dialyzers, no finalultrafilters, no additional pumps or external equipment and no externalsubstitution fluid are required.

The rate of filtration and backfiltration will be controlled by theresultant pressures due to the blood and dialysate flow rates. This isdiscussed in U.S. Pat. No. 6,406,631, issued Jun. 18, 2002, thedisclosure of which is incorporated herein by reference.

There are several advantages to the proposed double fiber bundledialyzer as compared with the prior art. First, the dialyzer accordingto the invention can be given a large membrane surface area that willresult in improved urea and creatinine removal.

The largest dialyzer commercially available today has a membrane surfacearea of 2.5 m². Dialyzers employing known ultrafiltration technologywould exhibit a tendency to clot if given a larger membrane surfacearea. In addition, if the filtration rate is too high in knowndialyzers, an alarm indicating a reverse ultrafiltration error will beproduced because the TMP (transmembrane pressure=average blood sidepressure−average dialysate side pressure) becomes negative and impliesfluid is fluxed across the membrane from the dialysate into the blood.In the past, when fluid quality was more questionable, this may havebeen a problem. Various dialysis machines measure TMP in different ways.Very few dialysis machines measure the blood in and blood out as well asthe dialysate in and dialysate out pressures to get a true TMP. Mostdialysis machines use the blood out and dialysate out pressures and anoffset to calculate the TMP.

However, the novel technology on which the present invention is basedmakes possible a dialyzer having a membrane surface area of 3.0 m² ormore. The double dialyzer configuration according to the presentinvention resolves the clotting issue as discussed herein, and alsoresolves the reverse ultrafiltration alarm problem by decreasing thedialysate out pressure due to the restricted passage between thedialysate compartments.

In addition, the rate of ultrafiltration and midsize molecule removalwill be greater in the dialyzer according to the invention than in priorart systems having the same dialyzer area and similar Kuf, Kuf being thecoefficient of ultrafiltration for the filter member, i.e., the rate ofplasma water fluid flux across the membrane, or fiber wall, per hour permmHg of transmembrane pressure (TMP). This is because the TMP isenhanced in the invention dialyzer by the two dialyzation chamberdesign.

Further, the dialysate distribution and resultant clearance will bebetter in dialyzers according to the invention, at least when crimpedfibers are used for the membranes. Specifically, crimped fibers resultin a more uniform dialysate flow throughout the dialyzer. This resultsin improved clearance of small molecules. Also, the provision of twoseparate dialysate compartments communicating via the restrictedpassage, or orifice, will help to redistribute the dialysate flows soany channeling, even with straight fibers, will be all but eliminated inthe second dialysate compartment.

Moreover, the system according to the present invention is constructedand operated to maintain the counter-current dialysate flow throughoutboth bundles whereas at least one existing dialyzer has a single chamberwith counter-current flow in one stage that contains a filter bundle andconcurrent flow, i.e., blood and dialysate flows in the same direction,in a second stage containing another bundle, which greatly reduces thediffusion gradient. In the operation of that dialyzer, it is necessaryto add substitution fluid directly into a space between the fiberbundles. If substitution fluid is not added, this dialyzer clots veryquickly. The second stage will have a lower small molecule removal ratesince the concentration gradient is smaller.

Furthermore, in prior art systems substitution fluid requires a separatefilter for the fluid generated on-line and a separate pump to controlinfusion, making the system more complicated and expensive to run than adialyzer according to the invention.

Specifically, dialyzers according to the invention are intended to beconnected to standard dialysis machines that are already in dialysisclinics to perform an HDF treatment. To perform any of the other HDFtreatments, prior art machines require a specialized structure that hasextra sensors to measure the amount of filtration, separate pumps toreturn the substitution fluid and extra filters since they reinfuse thesubstitution fluid either directly into the blood line or into theheader of the dialyzer. For example, these other systems will need tocalculate the volume going into the system (blood and dialysate) and thevolume coming out (blood and dialysate). The system needs to calculatethe rates of filtration and then must add the proper amount ofsubstitution fluid to the system to balance the fluid removed. So theequipment is complicated by balances or fluid control units that measurethe fluid exchanged. This also requires a pump to infuse thesubstitution fluid directly into the blood line. Our system uses theexisting fluid balancing system in the current machines. The fluidbalancing system can be a diaphragm pump such as in the Frensiusmachines or flow meter controlled system such as in the Gambro machines.

An advantage of the present invention is that the double fiber bundledialyzer can be used with any known dialysis machine with volumetriccontrol to perform an HDF treatment without needing to set up additionalinfusion lines, filters and/or pumps or units.

Improved midsize molecule clearance is achieved in a dialyzer accordingto the invention by increasing filtration and backfiltration. Morespecifically, midsize molecules are removed more effectively byfiltration (convection removal) and dialyzers according to the inventionenhance convective removal by the action of the restricted dialysatepassage 22 and by using the proper membranes.

Furthermore, a dialyzer according to the invention can be used inexisting dialysis machines without the need for additional hardware ormodifications.

For example, a dialyzer according to the invention can be used withknown dialysis machines, such as a standard Fresenius machine, on whicha dialyzer according to the invention was tested, in place of aconventional dialyzer, using the exact same set-up as for a standarddialysis treatment, including standard blood lines. The dialyzeraccording to the invention will automatically enhance the filtration andback filtration based on its design. Nearly all current dialysismachines have a place for an ultrafilter. This is a filter that filtersthe dialysate fluid prior to reaching the dialyzer. It is a component ofa dialysis machine, possibly not needed in systems according to thepresent invention. An ultrafilter is usually a hollow fiber filtersimilar to a standard dialyzer, but is designed to have the fluiddiffuse across the fibers (filtration) and then flow to the dialyzer.All machines marketed within the past 5 years or more have a built inultrafilter (also called an endotoxin filter).

The double fiber bundle dialyzer according to the invention differs fromthe prior art (e.g., U.S. Pat. No. 5,700,372) in several ways. Oneimportant difference is that in the system according to the invention,blood passes through and exits the fibers of bundle 14, then enters alarge space, i. e., intermediate chamber 38, where the blood exiting allof the fibers of bundle 14 is mixed together before entering the fibersof bundle 12. No filtration, or back filtration, or substitution offluid occurs in intermediate chamber 38; only blood flows throughintermediate chamber 38.

Chamber 38 performs an important function that serves to eliminate, orat least minimize, the adverse effects of a common problem in dialysisknown as “channeling”. Channeling can occur on the dialysate side or theblood side of the fibers. Channeling on the blood side is when bloodflows through different fibers at different rates. In the fibers inwhich a relatively fast flow occurs, the fibers see more blood than dothe fibers in which a slower blood flow occurs, although ultrafiltrationoccurs from all of the fibers. In the fibers experiencing slow bloodflow, while plasma water is being removed by ultrafiltration (raisingthe hematocrit: the proportion of blood volume that is occupied by redblood cells), the blood will tend to clot and the fibers will becomeblocked. This results in more flow through the other fibers and areduction in the active filter surface area, i.e., the filter surfacearea participating in the filtering of toxins. A reduction in the activefilter surface area of the dialyzer will reduce the efficiency of thedialyzer and the treatment. At the same time, the reduction in theactive filter surface area causes a higher pressure at blood inlet 40,which in turn causes more ultrafiltration in the remaining fibers. Thishigher ultrafiltration will lead to more clotting.

Since systems according to the invention have two smaller bundles offibers separated by intermediate chamber 38, as the blood goes throughthe fibers of bundle 14 it becomes more concentrated (because ofultrafiltration). However, all of the blood exiting the fibers of bundle14 enters the common intermediate chamber 38 and mixes together. Thiswill include the blood that flowed slowly through one or more fibers andthe blood that flowed faster through other fibers. The blood enteringthe fibers of bundle 12 will, therefore, be more homogenous. Thepressure of the blood entering the fibers of bundle 12 will also be thesame at all of the fiber walls, leading to a more consistentbackfiltration and reconstitution of the blood returning to the body atnearly the same hematocrit at which it was pumped out of the body.

To summarize, intermediate chamber space 38 in the double fiber bundlesystem according to the invention acts to mix the blood while nofiltration, or back filtration, or substitution of fluid is occurring sothat the blood entering the fibers of bundle 12 is homogenous and atnearly the same pressure from one fiber to another.

An exemplary preferred embodiment of the invention may have thefollowing specific parameters:

Dimensions of each fiber: ID=180-200 μm; wall thickness=filter member35-50 μm; OD=250-300 μm; length=28 cm±3 cm;

Effective surface area of each fiber bundle=1.5 m²;

Number of fibers in each chamber, i. e., in each bundle=approximately9500 fibers +/−500 fibers, the exact number depending on the diameterand length of the fibers.

The pore size for toxin removal should be selected to produce as sharp adrop as possible in the elimination rate of molecules at 65,000 or66,000 Daltons (the universal mass unit or atomic mass unit). Little orno molecular weight substances above 65,000 or 66,000 Daltons should beremoved. This will minimize protein losses during treatment.

One nonlimiting example of the membrane material of the fibers inbundles 12 and 14 would be a product marketed by Asahi Kasei KurarayMedical Co., Ltd. under the trade names REXBRANE and Polysulfone APS, apolysulfone membrane with a hydrophilic gel layer.

The fibers should be crimped to enhance dialysate flow. This crimpinggives the fibers a form that follows a sinuous path along their length,which is the form of the REXBRANE fibers.

Each fiber bundle may have a KuF (Coefficient of Ultrafiltration) of20-26 ml/h/(mmHg TMP), TMP can be calculated as the average pressure onthe blood side of the membrane minus the average pressure on thedialysate side of the membrane. TMP is mostly determined by thehydrostatic pressure of the blood flow on the blood side of the membrane(favoring flux from the blood side to the dialysate side), the oppositepressure of the dialysate fluid on the dialysate side of the membrane(favoring dialysate fluid flux to the blood side) as well as theopposite pressure associated with the oncotic pressures (which is a formof osmotic pressure exerted by proteins in blood plasma that normallytends to pull water into the circulatory system) of the blood proteins(favoring fluid flux from the dialysate side to the blood side). As morefluid flows across a membrane from the blood side to the dialysate side,the oncotic pressures increase as the protein concentration increasesdue to less plasma water and a relatively higher protein concentration.

The true calculation of Kuf, therefore, can vary as a function of theprotein concentrations, dialysate flows, and blood flows. The Kuf rangegiven above was consistent for the specific embodiment tested using theFresenius 2008 series dialysis machine and the blood and dialysate flowstested blood flow=350−550 ml/min and dialysate flow=800 ml/min). Whenthe dialysate flow (Qd) is reduced to 500 ml/min, there is a drop in TMP(machine measured) of close to 100 mmHg. This is due to the increase inaverage dialysate side pressures. The incoming dialysate pressures arenearly the same at 800 and 500 ml/min dialysate flows, the pressuresbeing approximately 200 mmHg±dependent on blood flow.

The pressure drop between the inlet and outlet of the dialysatecompartment in chamber 2 is slight due to the presence of theconstricted passage between the dialysate compartments. The pressuredrop across the constricted passage is lower with a 500 ml/min flow ratesince the flow is lower. This yields a higher average pressure in thedialysate compartment of chamber 4 for a 500 ml/min dialysate flow thanfor an 800 ml/min flow. The higher pressure on the dialysate side ofchamber 4 yields a drop in TMP.

Also, the conventional volumetric controller (not shown) of the dialysismachine to which the dialyzer is connected, which makes sure that thedialysate volume entering via inlet 44 is the same as the volume thatleaves via outlet 46, can apply a slight negative pressure at outlet 46,thereby pulling fluid from the blood side to make the incoming andoutgoing volumes the same. Additional fluid removal is normallyprogrammed into the dialysis machine in order to remove the excess fluida patient consumes between treatments. This excess fluid removal iscontrolled by a separate pump in all dialysis machines and works inconjunction with the present invention.

The Kuf (coefficient of ultrafiltration) is calculated for the fibers ofbundle 14 only using human blood reconstituted with saline and bovinealbumin at a concentration of ˜6 g/dL (this also effects the measuredKuf. If it was measured with saline, the Kuf would be calculated to bemuch higher due to the lower viscosity and lack of blood proteins, i.e.albumin).

In chamber 2, the dialysate compartment pressure drop with Qd=800 ml/min(dialyzer with incoming dialysate from the associated machine andprovided with the restricted passage beneath common wall 20 as well asback filtration)=about 15 mmHg (this is a slight pressure drop due tothe constricted passage at the outlet of the dialysate compartment inchamber 2).

In chamber 4, the pressure drop across the dialysate compartment withQd=800 ml/min (with a large filtration volume from blood to dialysateside, the machine volume controller can cause a negative pressure at theoutlet 46)=about 55 mmHg, with or without negative pressure at outlet46, downstream of the restricted passage to outlet 46 (dialysate flowsin counter-current to blood flow).

Constricted passage 22 in common wall 20 between the dialysatecompartments in chambers 2 and 4 should preferably provide a pressuredrop of ˜100 mmHg with a Qd=800 ml/min, or a 50 mmHg drop with Qd=500ml/min.

The total dialysate pressure drop between inlet 44 and outlet 46 shouldbe about 170 mmHg. There is some variability dependent on blood flow,rate of filtration with backfiltration and access needle size used orcatheter type (which effects venous pressure of returning blood atoutlet 42).

The blood side pressure drop is dependent on blood flow and the size ofthe venous needle used to return the blood to the patient's body (usinga smaller venous needle will result in a higher pressure leaving chamber2), but can be approximated, for chamber 4, as a pressure drop, betweenchambers 34 and 38, of 40% of the pressure entering the dialyzer fibers(header pressure, chamber 34). For example, if the incoming pressure is402 mmHg and the outgoing is 240 mmHg this is a difference of 162 mmHg,or 40% (=162/402), and approximately a 65% pressure drop of the pressurein chamber 38 to the exit chamber 30 (pressure drop across Chamber 2).The pressure drop in Chamber 2 will vary dependent on blood flow, ahigher blood flow resulting in a higher pressure drop. In the operationof a dialyzer according to the invention, a pressure drop of 75% atblood flows of 550 ml/min and a pressure drop of 62% at blood flows of350 ml/min were measured.

The double dialyzer according to the invention has two separate bundlesof fibers for filtration, with fiber bundle headers at the ends of thechambers. Manifolds 24, 26 and 28 may be constituted by potting compoundbodies. U.S. Pat. No. 4,227,295 (Bodnar) and U.S. Pat. No. 5,700,372(Takesawa), the disclosures of which are incorporated herein byreference, describe common methods to manufacture dialyzers using thepotting compound to form manifolds. This method can be used in thefabrication of a dialyzer according to the present invention. The fibersenter and exit through these bodies so that the blood encounters someresistance upon entering the fibers and the resistance at the entry toeach fiber bundle aids filtration.

The potting compound is used to separate the internal pathways presentedby the fibers from the dialysate compartments. This is done by insertingthe fiber bundles into the dialyzer casing. Thus, a lower end header capwill be provided. The potting compound bodies are formed in place beforethe top and bottom header caps are put in place. To form the pottingcompound bodies, a special cap is clamped on each end of the casing andpotting compound (polyurethane material) is injected into the specialcaps and around the fibers. The chambers are usually spun in order todistribute the potting compound so as to reliably form seals between thedialysate side and blood side of each chamber. Since blood flowing outof the fibers of bundle 14 will flow through chamber 38 and into thefibers of bundle 12, potting compound seals will be formed around thefiber ends that will extend into chamber 38, as well as around the fiberends that will extend into compartments 30 and 34, after which the fiberbundle ends projecting from the potting compound bodies may be slicedoff. The header caps may then be assembled to the ends of the casing.

Two separate dialysate compartments are provided in order to be able toprovide the flow constriction 22 therebetween to control the rates offiltration and backfiltration. In fact, the flow constriction betweendialysate compartments, near the bottom of wall 20, is a key componentof the double dialyzer according to the invention. If the flowconstriction yields too low of a pressure drop, the machine will alarmfor low TMP because the average dialysate pressure will be too low forthe amount of filtration the system produces. If the pressure dropacross the flow constriction is too high (too small of a passage crosssection), the dialyzer could clot as the TMP of fiber bundle 14 inchamber 4 increases (because of very low dialysate pressures), causingadditional ultrafiltration of plasma water and hemoconcentrating theblood in chamber 4. By having two separate bundles of fibers for bloodand dialysate, it becomes possible to maintain a counter-current flowbetween dialysate and blood through the entire double dialyzer system,maximizing diffusive removal of blood toxins.

The parameters presented herin have been found to produce good results.However, variations are possible within the framework of the invention.For example, the membrane fibers can have a smaller ID, and/or thinnerwalls, and/or smaller or larger fiber membrane surface areas (e.g., 0.9to 1.8 m² for each bundle). It is possible to have a difference in areabetween the two fiber bundles. This could be, for example 1.3 m² forbundle 12 and 1.5 m2 for bundle 14, although this may make manufacturingmore difficult. Unequal surface areas may also have to be balanced bypossibly changing the filtration capability of the fiber bundles. If afiber bundle having a smaller surface area were provided in one chamber,this may need to be compensated with a higher filtration capability inorder to provide the correct filtration and backfiltration. If the innerdiameter of each fiber were made smaller, the result would be anincrease in pressure drop and an increase in filtration. There arenumerous possible configurations.

Other variations, such as lower Kuf of the fiber bundles with higherpressure drops of the inter-dialysate chamber constriction are alsopossible, as well as higher Kuf and lower pressure drops. However, suchvariations should be within a small range to reach the optimal 25% ofblood flow filtration. For example, a Kuf of 10 with a blood flow of 500ml/min would require a TMP of 750 mmHg; however the limit for TMPs forthe membranes is usually around 500 mmHg or they could break. Similarly,a Kuf of 30 requires a maximum TMP of 250 mmHg; however at a 500 ml/minblood flow rate, the minimum TMP achievable is about 300 mmHg. The TMPreferred to is the actual measured TMP at the inlet and outlet of bothblood side and dialysate side, not the machine calculated TMP.

The constricted passage 22 in wall 20 is important because if there wereno constriction, the pressure at dialysate outlet 46 would besubstantially equal to the pressure at dialysate inlet 44, so that therewould be less filtration with backfiltration. Therefore, clearance ofmiddle weight toxins would be reduced and there would also be problemswith the dialysis machine because the dialysate pressure at outlet 46would be higher than if the constricted passage was present. This higherpressure at outlet 46 will result in a reverse TMP alarm.

Also, a double fiber bundle with similar parameters but smaller totalmembrane surface areas (0.3 to 0.9 m² for each bundle) can be used toprovide a hemodiafiltration treatment at lower blood flows (200 ml/min)and lower dialysate flows (100-500 ml/min). The constricted passagebetween dialysate compartments will still be required in order to dropthe average of the dialysate side pressures to allow the double fiberbundle dialyzer system to run on standard equipment.

Distribution rings, or dialysate diverters, commonly used in this art,may also be provided near the inlet and outlet of dialysate ports 44 and46, below manifolds 24 and 26, and at the bottom of the chambers, abovemanifold 28, to aid in distribution of the dialysate around the fibers.Examples of such diverters are disclosed in U.S. Pat. Nos. 4,396,510;5,084,244; and 6,623,638, the disclosures of which are incorporatedherein by reference.

The casing shown in FIG. 2 is provided with diverters 52, 53, 54 and 55,which may be integral parts of the casing. Dialysate entering via inlet44 flows around diverter 52 and upwardly over the upper edge of diverter52 before entering the dialysate compartment in chamber 2. Similarly,dialysate exiting from passage 22 will flow around diverter 55 and thenunder the lower edge of diverter 55 before entering the dialysatecompartment in chamber 4. Diverters 53 and 54 are also used to aid indialysate flow distribution by forcing the fluid to flow from the centerof the dialyzer over the diverter to the periphery where dialysate willflow through restricted passage via diverter 53 and to port 46 viadiverter 54. Since channeling commonly occurs along the walls of thechambers, the diverters force the dialysate away from the walls to thecenter where the fibers are located.

This present invention may also be used with the specialized dialysismachines capable of delivering HDF treatments. The use of pre-dilutionHDF (fluid infused before entering the dialyzer) using the presentinvention as the dialyzer will deliver a rate of filtration equal to orgreater than the amount of filtration of which a standard HDF dialyzerin the same pre-dilution modality is capable.

While the description above refers to particular embodiments of thepresent invention, it will be understood that many modifications may bemade without departing from the spirit thereof. The accompanying claimsare intended to cover such modifications as would fall within the truescope and spirit of the present invention.

The presently disclosed embodiments are therefore to be considered inall respects as illustrative and not restrictive, the scope of theinvention being indicated by the appended claims, rather than theforegoing description, and all changes which come within the meaning andrange of equivalency of the claims are therefore intended to be embracedtherein.

What is claimed is:
 1. A dialyzer comprising: first and seconddialyzation chambers, and an intermediate chamber interposed betweensaid first and second dialyzation chambers, wherein, each of saiddialyzation chambers has opposed first and second ends; each of saiddialyzation chambers contains a filter member that separates saiddialyzation chamber into a blood compartment and a dialysatecompartment, each of said compartments extending between said first andsecond ends; said filter member in said first dialyzation chamber ismade of a filter material for filtering out plasma water from blood;said filter member in said second dialyzation chamber is made of afilter material for passing dialysate from said dialysate compartment tosaid blood compartment; said first dialyzation chamber has, at saidfirst end thereof, a blood inlet communicating with said bloodcompartment and a dialysate outlet communicating with said dialysatecompartment; said second dialyzation chamber has, at said first endthereof, a blood outlet communicating with said blood compartment and adialysate inlet communicating with said dialysate compartment; saidintermediate chamber extends between said second end of said firstdialyzation chamber and said second end of said second dialyzationchamber and communicates only with said blood compartments duringoperation of said dialyzer to perform blood dialysis; said blood anddialysate inlets and outlets are located to produce dialysate flows incounter-current to blood flows in both of said dialyzation chambers; andsaid first and second dialyzation chambers are constructed to provide adialysate flow path between said dialysate compartments at said secondends of said chambers, said dialysate flow path forming a constrictedpassage for dialysate that produces a dialysate pressure drop betweensaid second dialyzation chamber and said first dialyzation chamber,wherein said constricted passage is dimensioned such that, duringoperation of said dialyzer, the dialysate pressure drop between saidsecond dialyzation chamber and said first dialyzation chamber causesplasma water to be removed from blood in said blood compartment of saidfirst dialyzation chamber and causes dialysate to be filtered from saiddialysate compartment into said blood compartment of said seconddialyzation chamber.
 2. The dialyzer of claim 1, wherein each saidfilter member is composed of a fiber membrane bundle having a fibermembrane surface area, and the fiber membrane surface area of saidfilter in said first dialyzation chamber is different from the fibermembrane surface area of said filter in said second dialyzation chamber.3. The dialyzer of claim 2, wherein each said filter member has a fibermembrane surface area of 0.9 m² to 1.8 m².
 4. The dialyzer of claim 1,wherein each said filter member is composed of a fiber bundle having acoefficient of ultrafiltration (Kuf) of 20-26 ml/h/(mmHg transmembranepressure).